Effects of endogenous fluorescence from ex vivo human facial skin specimens in the pharmacokinetic study of a topical minocycline gel using two-photon excitation fluorescence (2PEF) and fluorescence lifetime imaging microscopy (FLIM) (Conference Presentation)

Maiko Hermsmeier; Sinyoung Jeong; Akira Yamamoto; Xin Chen; Usha Nagavarapu; Conor L. Evans; Kin F. Chan

doi:10.1117/12.2294403

14 March 2018 Effects of endogenous fluorescence from ex vivo human facial skin specimens in the pharmacokinetic study of a topical minocycline gel using two-photon excitation fluorescence (2PEF) and fluorescence lifetime imaging microscopy (FLIM) (Conference Presentation)

Maiko Hermsmeier, Sinyoung Jeong, Akira Yamamoto, Xin Chen, Usha Nagavarapu, Conor L. Evans, Kin F. Chan

Author Affiliations +

Proceedings Volume 10475, Visualizing and Quantifying Drug Distribution in Tissue II; 104750H (2018) https://doi.org/10.1117/12.2294403
Event: SPIE BiOS, 2018, San Francisco, California, United States

Abstract

The safety and efficacy of an investigational topical minocycline gel (BPX-01) has recently been studied in a Phase 2b trial for the treatment of acne vulgaris. As part of the drug development process, there was a need to determine if minocycline was delivered to the target tissue compartments, including the epidermis, hair follicle, and the sebaceous gland. While it was easier to demonstrate delivery on an ex vivo human skin model with an infinite dose, it was initially challenging to verify low-dose delivery with conventional fluorescence microscopy due to the high autofluorescence inherent to human skin. An integrating sphere screening approach was implemented along with conventional fluorescence microscopy to quantitatively and qualitatively assess endogenous fluorescence concurrently from numerous human facial skin specimens. Donor tissues were cut into 50-µm frozen sections, mounted onto microscope slides, and positioned on an inverted fluorescence microscope, sandwiched between the microscope’s 40x high NA objective lens and an external integrating sphere. The tissue sections were illuminated with UV excitation centered at 386 nm. For the first time, it was found that random samples from >40 human facial skin donors produced at least 5× differential in measurable autofluorescence. This observation has significant implications for the use of 2PEF microscopy and FLIM to visualize/quantify drug distribution; the endogenous autofluorescence may limit the detectability of the minocycline signature. Our studies indicated that a single daily dose of BPX-01 was detected in low autofluorescence skin specimens with FLIM, thus validating a novel imaging modality for future pharmacokinetic studies.

Conference Presentation

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Maiko Hermsmeier, Sinyoung Jeong, Akira Yamamoto, Xin Chen, Usha Nagavarapu, Conor L. Evans, and Kin F. Chan "Effects of endogenous fluorescence from ex vivo human facial skin specimens in the pharmacokinetic study of a topical minocycline gel using two-photon excitation fluorescence (2PEF) and fluorescence lifetime imaging microscopy (FLIM) (Conference Presentation)", Proc. SPIE 10475, Visualizing and Quantifying Drug Distribution in Tissue II, 104750H (14 March 2018); https://doi.org/10.1117/12.2294403

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KEYWORDS

Skin

Luminescence

Fluorescence lifetime imaging

Microscopy

Integrating spheres

Tissues

Microscopes

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